The annual meeting of the American College of Medical Genetics (ACMG) brings together a large proportion of basic and clinical investigators of rare genetic diseases. The organizers propose a series of workshops to be held in conjunction with ACMG meetings to consider issues related to identifying needs and opportunities for collaborative research involving rare genetic diseases (RGDs) associated with birth defects, mental retardation and developmental disabilities, and would set the stage for clinical and translational research. RGDs present many challenges to the development of effective research plans. These include infrastructure to identify and register patients with RGDs, their associated databases, identification and/or collection of biological specimens, coordination of rapidly evolving therapeutic interventions, and the coordination of studies of a usually limited number of experts involved with any individual rare condition with expertise from correlative sciences and other specialties. A coordinated and collaborative group would facilitate research into the epidemiology, intervention, and prevention of these rare conditions. It would allow for the integration of the many complementary programs overseen by non-NIH governmental organizations and agencies and, in association with currently funded NIH initiatives such as the Mental Retardation Research Centers and the National Children's Study, be highly synergistic with regard to RGD research. The annual workshops over the five years of this application would evaluate the existing models for facilitating collaborative research such as the consortium and cooperative group models. Specific diseases or classes of diseases would be used to identify the research gaps in the current system, the types of research that would be enabled, and the issues that rare genetic diseases raise that drive the need for collaborative research. The workshops would bring together representatives of government agencies, basic and clinical researchers, consumers and families, women, minorities, and underserved populations and geneticists. The first workshop in March 2004 would focus on the current models for collaborative research, the needs and potential benefits of collaborative research for these conditions, and assess collaborative research systems for a specific disease such as the lysosomal storage diseases or cystic fibrosis.